Striatum Gene Expression Correlates for HAND_BASELINE measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The HAND_BASELINE measures Handling induced convulsion baseline under the domain Ethanol HIC. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
cocaine and amphetamine-regulated transcript QTL 2 (Crq2) spans 99.841331 - 149.841331 Mbp (NCBI Build 37) on Chr 4. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
QTL for chronic alcohol withdrawal severity on Chr4 at D4Mit186 (95.43 Mbp , Build 37)
Description:
chronic alcohol withdrawal severity spans 70.43 - 120.43 Mbp (NCBI Build 37) on Chr4. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Bergeson SE, Kyle Warren R, Crabbe JC, Metten P, Gene Erwin V, Belknap JK
Striatial Gene Expression DID Mice Common between 2 line
Description:
Differential expression in stratum between HS/NPT controls and the selected lines was calculated using the eBayes modified t-statistic and further adjusted using the false discovery rate. At an FDR 0.1, we detected 1,430 (HDID-1 vs. HS/NPT) and 301 (HDID-2 vs. HS/NPT) differentially expressed transcripts. One hundred and four transcripts were differentially expressed in both comparisons; 94 of these had the same directionality.
WGCNA on BXD Coexpression Network Interactions Associated with Predisposition to Alcohol Consumption.Column p-value and uploaded Nucleus Accumbens, navajowhite1 module.
Authors:
Vanderlinden LA, Saba LM, Kechris K, Miles MF, Hoffman PL, Tabakoff B
Genes that have regions with differential 5-hydroxymethylcytosine (5hmC) levels in response to cocaine in adult (8-10 week) male C57BL/6J mice. 5hmC levels were measured via 5hmC-seq. Data taken from Supplementary Table 2. Values presented are p-values. Data available at GEO with accession number GSE63749.
Authors:
Jian Feng, Ningyi Shao, Keith E Szulwach, Vincent Vialou, Jimmy Huynh, Chun Zhong, Thuc Le, Deveroux Ferguson, Michael E Cahill, Yujing Li, Ja Wook Koo, Efrain Ribeiro, Benoit Labonte, Benjamin M Laitman, David Estey, Victoria Stockman, Pamela Kennedy, Thomas Couroussé, Isaac Mensah, Gustavo Turecki, Kym F Faull, Guo-li Ming, Hongjun Song, Guoping Fan, Patrizia Casaccia, Li Shen, Peng Jin, Eric J Nestler
Alcohol use disorder (AUD) is a complex psychiatric disorder with strong genetic and environmental risk factors. We studied the molecular perturbations underlying risky drinking behavior by measuring transcriptome changes across the neurocircuitry of addiction in a genetic mouse model of binge drinking. Sixteen generations of selective breeding for high blood alcohol levels after a binge drinking session produced global changes in brain gene expression in alcohol-naïve High Drinking in the Dark (HDID-1) mice. Using gene expression profiles to generate circuit-level hypotheses, we developed a systems approach that integrated regulation of gene coexpression networks across multiple brain regions, neuron-specific transcriptional signatures, and knowledgebase analytics. Whole-cell, voltage-clamp recordings from nucleus accumbens shell neurons projecting to the ventral tegmental area showed differential ethanol-induced plasticity in HDID-1 and control mice and provided support for one of the hypotheses. There were similarities in gene networks between HDID-1 mouse brains and postmortem brains of human alcoholics, suggesting that some gene expression patterns associated with high alcohol consumption are conserved across species. This study demonstrated the value of gene networks for data integration across biological modalities and species to study mechanisms of disease.
Authors:
Laura B Ferguson, Lingling Zhang, Daniel Kircher, Shi Wang, R Dayne Mayfield, John C Crabbe, Richard A Morrisett, R Adron Harris, Igor Ponomarev
Alcohol use disorder (AUD) is a complex psychiatric disorder with strong genetic and environmental risk factors. We studied the molecular perturbations underlying risky drinking behavior by measuring transcriptome changes across the neurocircuitry of addiction in a genetic mouse model of binge drinking. Sixteen generations of selective breeding for high blood alcohol levels after a binge drinking session produced global changes in brain gene expression in alcohol-naïve High Drinking in the Dark (HDID-1) mice. Using gene expression profiles to generate circuit-level hypotheses, we developed a systems approach that integrated regulation of gene coexpression networks across multiple brain regions, neuron-specific transcriptional signatures, and knowledgebase analytics. Whole-cell, voltage-clamp recordings from nucleus accumbens shell neurons projecting to the ventral tegmental area showed differential ethanol-induced plasticity in HDID-1 and control mice and provided support for one of the hypotheses. There were similarities in gene networks between HDID-1 mouse brains and postmortem brains of human alcoholics, suggesting that some gene expression patterns associated with high alcohol consumption are conserved across species. This study demonstrated the value of gene networks for data integration across biological modalities and species to study mechanisms of disease.
Authors:
Laura B Ferguson, Lingling Zhang, Daniel Kircher, Shi Wang, R Dayne Mayfield, John C Crabbe, Richard A Morrisett, R Adron Harris, Igor Ponomarev
Alcohol transcriptome changes in mice microglia p-value
Description:
Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer’s disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated prefrontal cortical microglia in response to recurring bouts of voluntary alcohol drinking behavior. The voluntary ethanol paradigm utilizes long-term consumption ethanol that results in escalated alcohol intake and altered cortical plasticity that is seen in humans. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Genes within this group are involved in toll-like receptor signaling and transforming growth factor beta signaling. Network connectivity of this group identified Siglech as a putative hub gene and highlighted the potential importance of proteases in the microglial response to chronic ethanol. In conclusion, we identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, and possibly other CNS disorders.
Authors:
Gizelle M McCarthy, Sean P Farris, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
Alcohol transcriptome changes in mice microglia total homogenate p-value
Description:
Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer’s disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated prefrontal cortical microglia in response to recurring bouts of voluntary alcohol drinking behavior. The voluntary ethanol paradigm utilizes long-term consumption ethanol that results in escalated alcohol intake and altered cortical plasticity that is seen in humans. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Genes within this group are involved in toll-like receptor signaling and transforming growth factor beta signaling. Network connectivity of this group identified Siglech as a putative hub gene and highlighted the potential importance of proteases in the microglial response to chronic ethanol. In conclusion, we identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, and possibly other CNS disorders.
Authors:
Gizelle M McCarthy, Sean P Farris, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
GeneWeaver